肿瘤细胞中低聚糖基化粘蛋白-1表达的无标记体内分子成像
Label-free in vivo molecular imaging of underglycosylated mucin-1 expression in tumour cells.
作者信息
Song Xiaolei, Airan Raag D, Arifin Dian R, Bar-Shir Amnon, Kadayakkara Deepak K, Liu Guanshu, Gilad Assaf A, van Zijl Peter C M, McMahon Michael T, Bulte Jeff W M
机构信息
1] Division of MR Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, the Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
1] Division of MR Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, the Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA [3] Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
出版信息
Nat Commun. 2015 Mar 27;6:6719. doi: 10.1038/ncomms7719.
Alterations in mucin expression and glycosylation are associated with cancer development. Underglycosylated mucin-1 (uMUC1) is overexpressed in most malignant adenocarcinomas of epithelial origin (for example, colon, breast and ovarian cancer). Its counterpart MUC1 is a large polymer rich in glycans containing multiple exchangeable OH protons, which is readily detectable by chemical exchange saturation transfer (CEST) MRI. We show here that deglycosylation of MUC1 results in >75% reduction in CEST signal. Three uMUC1(+) human malignant cancer cell lines overexpressing uMUC1 (BT20, HT29 and LS174T) show a significantly lower CEST signal compared with the benign human epithelial cell line MCF10A and the uMUC1(-) tumour cell line U87. Furthermore, we demonstrate that in vivo CEST MRI is able to make a distinction between LS174T and U87 tumour cells implanted in the mouse brain. These results suggest that the mucCEST MRI signal can be used as a label-free surrogate marker to non-invasively assess mucin glycosylation and tumour malignancy.
黏蛋白表达和糖基化的改变与癌症发展相关。糖基化不足的黏蛋白-1（uMUC1）在大多数上皮来源的恶性腺癌（如结肠癌、乳腺癌和卵巢癌）中过表达。其对应物MUC1是一种富含聚糖的大分子聚合物，含有多个可交换的OH质子，可通过化学交换饱和转移（CEST）磁共振成像（MRI）轻松检测到。我们在此表明，MUC1的去糖基化导致CEST信号降低>75%。三种过表达uMUC1的uMUC1(+)人恶性癌细胞系（BT20、HT29和LS174T）与良性人上皮细胞系MCF10A和uMUC1(-)肿瘤细胞系U87相比，CEST信号显著更低。此外，我们证明，体内CEST MRI能够区分植入小鼠脑内的LS174T和U87肿瘤细胞。这些结果表明，mucCEST MRI信号可作为一种无标记替代标志物，用于无创评估黏蛋白糖基化和肿瘤恶性程度。
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